Treatment of the two chronic inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC) is still hampered, because we do not understand the pathophysiological processes behind them. Are they caused by a normal inflammatory response reacting towards a foreign agent, or are they caused by an abnormal inflammatory response against a common or even universal agent? Our only choices at present are symptomatic treatments, including immunosuppressive drugs. To make the necessary controlled testing of new immunosuppressive drugs ethically acceptable, we have to choose carefully between different designs: comparing a new drug against placebo in overall treatment failures, to add the new drug or placebo to ongoing treatment (addition design), or to apply a classical group comparison between test drug and placebo in moderately active cases. There exists a strong need for extension of indications for immunosuppressive and anti-inflammatory treatments: to be able to treat long-term instead of short-term, to do without extensive surgery in some UC cases, to treat severe UC cases with isolated distal involvement, to treat CD patients with short bowel syndrome, and to treat CD patients with fistulae and severe extra-intestinal manifestations. Future drug treatment of IBD will probably still be based on immunosuppressive and anti-inflammatory drugs, while waiting for a pathophysiological breakthrough in these two diseases.